Name: 330786-34-0|4-((3-Chloro-4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylic acid|95+%
Brand: Ambeed
SKU: A382844
Price: 22.0 USD
Availability: InStock
Rating: 94 (35 reviews)

1
[ 79-37-8 ]
[ 330786-34-0 ]
[ 330786-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; N,N-dimethyl-formamide	158.1 EXAMPLE 158 (1) A suspension of 4-(3-chloro-4-methoxybenzylamino)-5-carboxy-2-methylthiopyrimidine (154.0 mg) obtained in Example 149 (1) in methylene chloride (5 ml) is treated with oxalyl chloride (119 μl) at room temperature, and thereto is added N,N-dimethylformamide. The mixture is stirred for one hour, and the solvent is evaporated under reduced pressure. The residue is treated with ether, and kept in a refrigerator overnight. The volatile materials are removed under reduced pressure, and the residue is treated with an excess amount of diazomethane at 0° C. and kept in a refrigerator overnight. The reaction is quenched with methanol, and the mixture is purified by silica gel chromatography (solvent; hexane:ethyl acetate=2:1) to give 4-(3-chloro-4-methoxybenzylamino)-5-(diazomethylcarbonyl)-2-methylthiopyrimidine (21.5 mg) as pale yellow solid, IR (Nujol): 3277, 2115, 1607, 1567, 1461, 1377, 1357, 1141 cm1, MS (m/z): 364 (MH+), m.p. 162-165° C. (dec.).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2003/32647, 2003, A1

2
[ 330785-81-4 ]
[ 330786-34-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With methanol; sodium hydroxide; at 20 - 30℃; for 4.5h;	ethyl 4-[(3-chloro-4-methoxybenzyl)amino]-2-methylthiopyrimidine-5carboxylate obtained in the step S3 (98.0 g, 0.27 mol) was dissolved in 300 mL of methanol.Temperature control below 30 C,After dropping a 16% aqueous solution of NaOH (150 mL, 0.71 mol),After reacting at room temperature for 4.5 h, methanol was distilled off under reduced pressure.Adjust the pH to 6 with concentrated hydrochloric acid,A large amount of gray solid was precipitated, and after stirring for 1 hour, it was suction filtered and washed with water.Vacuum drying gave a gray powder (97.7 g, 94%).
93.3%	With sodium hydroxide; In ethanol; at 20 - 55℃;	The product VI obtained in the step (1) is added to 450 ml of ethanol, heated and stirred at 50-55 C until the temperature of the material is cooled to 20-30 C, 105 ml of 10% sodium hydroxide solution is added and stirred at 20-30 C for 1.5-2 hours. The mixture was added dropwise with 10% citric acid solution to adjust the pH of the solution to about 4 ~ 5. A large amount of solid was precipitated and the mixture was stirred at 20-30 C for 1-1.5h. The solid was washed with water and dried under vacuum at 50 C for 3h to obtain 14.0g of white solid. Yield 93.3%.
87.6%		50ml three reaction flask was added 19 (1.30g, 3.53mmol) was added at room temperature a mixed solution of tetrahydrofuran and methanol (v / v = 1: 1, 10 ml). After stirring for 15 minutes, an aqueous solution of potassium hydroxide (346 mg, 6.18 mmol, dissolved in 1.7 ml of water) was added and the mixture was stirred at room temperature overnight. TLC showed the reaction was completed. The reaction mixture was concentrated by heating and the organic phase was evaporated. The aqueous phase was washed twice with methylene chloride. The aqueous phase was slowly added dropwise with 1 M dilute hydrochloric acid. The pH of the solution was adjusted to 2-3 and extracted three times with ethyl acetate. The organic phases were combined, dried and filtered, and concentrated by rotary evaporation to give Compound 21 (1.05 g, 87.6%) as a white powder.

76%	With water; sodium hydroxide; In tetrahydrofuran; methanol; at 60℃; for 10.0h;	In a mixture of water (10 mL), methanol (30 mL) and THF (30 mL) were dissolved ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio) pyrimidine-5-carboxylate (6.0 g, 16.3 mmol) and sodium hydroxide (1.14 g, 28.57 mmol). The reaction was conducted for 10 h at 60 C. The reaction mixture was cooled to ambient temperature and adjusted to a pH of 4 by addition of dilute hydrochloric acid dropwise. A solid was precipitated, filtrated, washed with methanol and dried to give 4-((3-chloro-4-methoxybenzyl)amino)-2 -(methylthio)pyrimidine-5-carboxylic acid (4.2 g, 76 % yield).
	With sodium hydroxide; citric acid; In water; dimethyl sulfoxide;	(1) A suspension of 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine (2.00 g) obtained in Example 1 (1) in dimethylsulfoxide (10 ml) is treated with 10% aqueous sodium hydroxide solution (10 ml) at room temperature. To the reaction mixture is added dimethylsulfoxide (5 ml), and the mixture is stirred at room temperature overnight. To the resulting colorless solution is added citric acid until the solution becomes acidic. To the solution is added an excess amount of water (about 50 ml), and the resulting precipitates are collected by filtration. The precipitates are washed with isopropyl alcohol and isopropyl ether successively, and dried under reduced pressure to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine (1.864 g) as pale yellow impalpable powder, m.p. 238-240 C. (dec.).
	With sodium hydroxide; In dimethyl sulfoxide;	Example 79 2-Methylthio-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine (prepared in Example 67-(1)) 2.00 g is suspended in dimethyl sulfoxide 10 ml, and the suspension is treated with a 10% aqueous sodium hydroxide solution 10 ml. The reaction mixture is still in suspension even 6 hours later. After addition of dimethyl sulfoxide 5 ml the mixture is stirred at room temperature over night. The resulting clear reaction solution is acidified with citric acid. The excess water (about 50 ml) is added thereto and resulting precipitate is filtered, washed with isopropylalcohol and then isopropyl ether, and concentrated in vacuo to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine as a pale yellow impalpable powder, 1.864 g. mp 238-240 C. (decomposition)
87 g	With water; sodium hydroxide; In methanol;Reflux;	To 600ml of methanol was added bOg of ethyl 4-[(3-chloro-4-methoxybenzyl) amino] -2-(methyl sulfanyl) pyrimidine-5 -carboxylate (Referential Example 1) and an aqueous solution of sodium hydroxide (15g of NaOH in 140rn1 of water). The reaction mixture was heated to reflux temperature. After completion of reaction, the pH of mixture was adjusted to 1-2 using concentrated hydrochloric acid followed by stirring the mixture for 1 hour at 10-15C. The solid product obtained was filtered, washed sequentially with water and methanol, and dried overnight at 70-75C to get 87g of 4-[(3-chloro-4-methoxybenzyl) aminoj-2-(methyl sulfanyl) pyrimidine-5- carboxylic acid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 5460 - 5465
[2]Patent: CN108707141,2018,A .Location in patent: Paragraph 0027; 0032; 0036; 0041; 0045; 0050
[3]Patent: CN104059025,2017,B .Location in patent: Paragraph 0039; 0040; 0041; 0056-0058; 0072-0074; 0088-0090
[4]Patent: CN104710411,2017,B .Location in patent: Paragraph 0025; 0062; 0063; 0064; 0065; 0066; 0067-0069
[5]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 1431 - 1435
[6]Patent: EP2886540,2015,A1 .Location in patent: Paragraph 0170; 0171
[7]Patent: US2003/32647,2003,A1
[8]Patent: US2004/142930,2004,A1
[9]Patent: WO2015/177807,2015,A1 .Location in patent: Page/Page column 14; 15

3
[ 3731-51-9 ]
ethylene dichloride hydrochloride [ No CAS ]
[ 330786-34-0 ]
[ 372113-63-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol In <i>N</i>-methyl-acetamide	80 Example 80 Example 80 2-Methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine (prepared in Example 79) 0.500 g, 2-pyridylmethylamine 0.1749 g, 1-hydroxybenzotriazole 0.1987 g, 1,2-dichloroethane hydrochloride 0.3102 g and anhydrous dimethylformamide 5 ml are mixed together and stirred at 0° C. overnight and triturated with ethyl acetate-isopropyl ether to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-pyridylmethyl)carbamoyl]pyrimidine as a colorless powder, 0.5966 g. mp 143-144.5° C.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2004/142930, 2004, A1

4
[ 586-98-1 ]
[ 330786-34-0 ]
[ 4136-95-2 ]
[ 372113-64-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 2-(Dimethylamino)pyridine; triethylamine In tetrahydrofuran; water; ethyl acetate	81 Example 81 Example 81 A mixture of 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine (prepared in Example 79) 0.100 g and triethylamine 82 μl in tetrahydrofuran 2.0 ml is treated under room temperature with 2,4,6-trichlorobenzoyl chloride 51 μl and then dimethylaminopyridine about 1 mg is added thereto, followed by stirring for 10 minutes. After addition of 2-pyridinemethanol 31 μl, the mixture is stirred for 12 hours. Ethyl acetate and water are added thereto and the organic layer is separated, washed with sodium hydrogen carbonate solution, brine. The organic layer is dried over anhydrous sodium sulfate and in vacuo. The residue is purified with silica gel chromatography (solvent; chloroform:ethyl acetate=5:1-2:1) and recrystallized from ethyl acetate-isopropyl ether to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-(2-pyridylmethoxycarbonyl)pyrimidine as a colorless needle, 0.5183 g. mp 117-118° C.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2004/142930, 2004, A1

5
[ 330786-34-0 ]
C₂₂H₂₅ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

6
[ 330786-34-0 ]
C₂₄H₂₇ClN₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

7
[ 330786-34-0 ]
C₂₄H₂₇ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

8
[ 330786-34-0 ]
C₂₅H₂₉ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

9
[ 330786-34-0 ]
C₂₉H₂₉ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

10
[ 330786-34-0 ]
[ 330784-22-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

11
[ 330786-34-0 ]
C₂₃H₂₆ClN₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

12
[ 330786-34-0 ]
[ 330784-47-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C
	Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane
	Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane 4.1: sulfuric acid / ethanol / Reflux 4.2: 5 h

	Multi-step reaction with 5 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane 4.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 5.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 5 °C 5.2: 60 - 70 °C
	Multi-step reaction with 2 steps 1.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 20 - 30 °C 2.1: triethylamine / 1 h / 20 - 30 °C
	Multi-step reaction with 3 steps 1.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 20 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 0.5 h / -15 - -10 °C 3.1: triethylamine / ethyl acetate / 20 - 30 °C
	Multi-step reaction with 3 steps 1.1: p-toluenesulfonyl chloride; potassium carbonate / acetonitrile / 20 °C 1.2: 0.33 h / 20 °C 2.1: sodium hypochlorite / acetonitrile; ethyl acetate / 15 - 30 °C 3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 0 °C 3.2: 4 h / 20 °C
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide; <i>N</i>,<i>N</i>-dimethyl-aniline / 7 h / 60 °C 2: acetic acid; dihydrogen peroxide / 4 h / 65 - 80 °C 3: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 5 h / 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]
[2]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[3]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[4]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[5]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B
[6]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B
[7]Current Patent Assignee: ARROMAX PHARMATECH SUZHOU CO LTD - CN104710411, 2017, B
[8]Current Patent Assignee: CHINA UNION CHEMPHARMA SUZHOU - CN108707141, 2018, A

13
[ 330786-34-0 ]
C₂₁H₂₈ClN₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

14
[ 330786-34-0 ]
N-((trans)-4-hydroxylcyclohexan-1-yl)-4-((3-chloro-4-methoxybenzyl)amino)-2-((S)-2-(hydroxymethyl)tetrahydropyrrole-1-yl)-5-pyrimidine formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

15
[ 330786-34-0 ]
C₂₀H₂₀ClN₅O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

16
[ 330786-34-0 ]
4-[(3-chloro-4-methoxybenzyl)amino]-2-methanesulfonyl-N-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C
	Multi-step reaction with 2 steps 1.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 20 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 0.5 h / -15 - -10 °C
	Multi-step reaction with 2 steps 1.1: p-toluenesulfonyl chloride; potassium carbonate / acetonitrile / 20 °C 1.2: 0.33 h / 20 °C 2.1: sodium hypochlorite / acetonitrile; ethyl acetate / 15 - 30 °C

Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide; <i>N</i>,<i>N</i>-dimethyl-aniline / 7 h / 60 °C 2: acetic acid; dihydrogen peroxide / 4 h / 65 - 80 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]
[2]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B
[3]Current Patent Assignee: ARROMAX PHARMATECH SUZHOU CO LTD - CN104710411, 2017, B
[4]Current Patent Assignee: CHINA UNION CHEMPHARMA SUZHOU - CN108707141, 2018, A

17
[ 330786-34-0 ]
C₁₇H₂₁ClN₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

18
[ 330786-34-0 ]
C₂₀H₂₅ClN₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

19
[ 3731-51-9 ]
[ 330786-34-0 ]
[ 372113-63-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

20
[ 330786-34-0 ]
[ 75985-45-4 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 60℃;	In DMF (60 mL) were dissolved 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio) pyrimidine-5-carboxylic acid (1.0 g, 2.95 mmol), <strong>[75985-45-4]pyrimidine 2-ylmethylamine</strong> (570 mg, 5.22 mmol) and HATU (2-(7-azabenzotuazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 2.64 g, 6.96 mmol), then DIEA (152 mg, 1.2 mmol) was added dropwisely. The reaction mixture was stirred at 60 C overnight, extraced with DCM after water was added and washed with brine. The organic phase was dried over sodium sulfate. The solvent was removed by rotary evaporation, then the solid obtained was purifide by silica gel column chromatography (DCM / methanol = 50 / 1) to give 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide (350 mg, 13 % yield).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 5460 - 5465
[2]Patent: EP2886540,2015,A1 .Location in patent: Paragraph 0172; 0173

21
[ 330786-34-0 ]
[ 156-87-6 ]
C₁₇H₂₁ClN₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

22
[ 330786-34-0 ]
[ 27489-62-9 ]
C₂₀H₂₅ClN₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]

23
[ 5909-24-0 ]
[ 330786-34-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / water; ethanol / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 20 °C
	Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 0.25 h / 20 °C / Cooling with ice 1.2: 20 °C 2.1: sodium hydroxide; water / tetrahydrofuran; methanol / 10 h / 60 °C

	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 10 h / 20 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 10 h / 60 °C
	Multi-step reaction with 2 steps 1: tetrabutylammomium bromide; sodium carbonate / dichloromethane; water / 25 - 30 °C 2: water; sodium hydroxide / methanol / Reflux
	Multi-step reaction with 2 steps 1: triethylamine / ethyl acetate / 0 - 30 °C 2: sodium hydroxide / ethanol / 20 - 55 °C
	Multi-step reaction with 2 steps 1.1: triethylamine / N,N-dimethyl-formamide / 4 h / 20 °C / Cooling with ice 2.1: tetrahydrofuran / 0.25 h / 20 °C 2.2: 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / acetone / 3 h / 20 °C 2: methanol; sodium hydroxide / 4.5 h / 20 - 30 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]
[2]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]
[3]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1
[4]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1
[5]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[6]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B
[7]Current Patent Assignee: ARROMAX PHARMATECH SUZHOU CO LTD - CN104710411, 2017, B
[8]Current Patent Assignee: CHINA UNION CHEMPHARMA SUZHOU - CN108707141, 2018, A

24
[ 115514-77-7 ]
[ 330786-34-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / water; ethanol / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 10 h / 20 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 10 h / 60 °C

	Multi-step reaction with 2 steps 1: tetrabutylammomium bromide; sodium carbonate / dichloromethane; water / 25 - 30 °C 2: water; sodium hydroxide / methanol / Reflux
	Multi-step reaction with 2 steps 1: triethylamine / ethyl acetate / 0 - 30 °C 2: sodium hydroxide / ethanol / 20 - 55 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Murakami, Michino; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5460 - 5465]
[2]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]
[3]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1
[4]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[5]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B

25
[ 330786-34-0 ]
[ 330785-86-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With manganese(IV) oxide In dichloromethane at 20℃;

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

26
[ 330786-34-0 ]
[ 330785-87-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

27
[ 330786-34-0 ]
[ 330784-23-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: tetrahydrofuran; diethyl ether / -78 °C 3.2: 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

28
[ 330786-34-0 ]
[ 372114-66-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: n-butyllithium / tetrahydrofuran; diethyl ether / -78 °C 3.2: 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

29
[ 330786-34-0 ]
[ 330785-94-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: tetrahydrofuran / 0 °C 3.2: 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

30
[ 330786-34-0 ]
[ 372113-70-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: n-butyllithium / tetrahydrofuran / -78 °C 2.2: 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

31
[ 330786-34-0 ]
[ 372113-71-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: n-butyllithium / tetrahydrofuran / -78 °C 2.2: 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 3.2: 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

32
[ 330786-34-0 ]
[ 330785-78-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: tetrahydrofuran / 0 °C 3.2: 20 °C 4.1: ethanol / 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

33
[ 330786-34-0 ]
[ 454486-73-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: manganese(IV) oxide / dichloromethane / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

34
[ 330786-34-0 ]
8-(3-Chloro-4-methoxy-benzyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: manganese(IV) oxide / dichloromethane / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 20 °C 3: sodium hydride / mineral oil; methanol / 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

35
[ 330786-34-0 ]
[ 454486-81-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: manganese(IV) oxide / dichloromethane / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 20 °C 3: copper(l) cyanide / tetrahydrofuran / 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

36
[ 330786-34-0 ]
8-(3-Chloro-4-methoxy-benzyl)-2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-5-methyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 20 °C 3.1: copper(l) cyanide / tetrahydrofuran / 0 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 4.2: 60 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

37
[ 330786-34-0 ]
(S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 20 °C 3.1: sodium hydride / mineral oil; methanol / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 4.2: 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

38
[ 330786-34-0 ]
8-(3-Chloro-4-methoxy-benzyl)-2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 20 °C 3.1: copper(l) cyanide / tetrahydrofuran / 0 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 4.2: 60 °C 5.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / 1,4-dioxane / 60 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

39
[ 330786-34-0 ]
2-methylthio-5-(1-methyl-2-imidazolyl)-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: n-butyllithium / tetrahydrofuran / -78 °C 2.2: 20 °C 3.1: sodium hydride / mineral oil; toluene / 100 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

40
[ 330786-34-0 ]
(S)-2-(2-Hydroxymethyl-1-pyrrolidinyl)-5-(1-methyl-2-imidazolyl)-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: n-butyllithium / tetrahydrofuran / -78 °C 2.2: 20 °C 3.1: sodium hydride / mineral oil; toluene / 100 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 4.2: 0 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

41
[ 330786-34-0 ]
(S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-5-(pyridin-2-yl)-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: n-butyllithium / tetrahydrofuran; diethyl ether / -78 °C 3.2: 20 °C 4.1: sodium hydride / mineral oil; toluene / 100 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

42
[ 330786-34-0 ]
(S)-2-(2-Hydroxymethyl-1-pyrrolidinyl)-5-[2-(4-morpholinyl)ethyl]-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: manganese(IV) oxide / dichloromethane / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 0 °C 2.2: 0 °C 3.1: tetrahydrofuran / 0 °C 3.2: 20 °C 4.1: ethanol / 20 °C 5.1: n-butyllithium; N-cyclohexyl-cyclohexanamine / tetrahydrofuran / 20 °C

Reference： [1]Sakamoto, Toshiaki; Koga, Yuichi; Hikota, Masataka; Matsuki, Kenji; Mochida, Hideki; Kikkawa, Kohei; Fujishige, Kotomi; Kotera, Jun; Omori, Kenji; Morimoto, Hiroshi; Yamada, Koichiro [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1431 - 1435]

43
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-((5-methylpyrazin-2-yl)methyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 18 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

44
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(4-fluorobenzyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 18 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

45
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfinyl)pyrimidine-5-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 5h; Cooling with ice;	2.1 (1) Preparation: 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfinyl)pyrimidine -5-carboxylic acid In DCM (20 mL) was dissolved 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio) pyrimidine-5-carboxylic acid (200 mg, 0.59 mmol). The solution was cooled in an ice bath and m-CPBA (101 mg, 0.59 mmol) was then added. The reaction was warmed to ambient temperature for 5 h. Then water was added and the reaction mixture was extracted with DCM. The organic phase was dried and concentrated to give a solid. The product was used in the subsequent procedure without further purification.

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1 Location in patent: Paragraph 0183; 0184

46
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

47
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(pyridin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 18 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

48
[ 330786-34-0 ]
N-benzyl-4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfinyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

49
[ 330786-34-0 ]
tert-butyl 4-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamido)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

50
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(piperdin-4-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / water; tetrahydrofuran / 8 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

51
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-N-(pyrimidin-2-ylmethyl)-2-(7-azaspiro[3.5]nonan-7-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 8 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

52
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-N-(pyrimidin-2-ylmethyl)-2-(6-azaspiro[2.5]octan-6-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 8 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

53
[ 330786-34-0 ]
N-benzyl-4-((3-chloro-4-methoxybenzyl)amino)-2-(2,6-diazaspiro[3.4]octan-6-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C 3: triethylamine / tetrahydrofuran / 4 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

54
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(7-methyl-2,7-diazaspiro[4.5]decan-2-yl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 4 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

55
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

56
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 4 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

57
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 8 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

58
[ 330786-34-0 ]
N-benzyl-4-((3-chloro-4-methoxybenzyl)amino)-2-(5-azaspiro [2.4]heptan-5-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C 3: triethylamine / tetrahydrofuran / 18 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

59
[ 330786-34-0 ]
N-benzyl-2-(3-oxo-8-azabicyclo[3.2.1]octan-8-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

60
[ 330786-34-0 ]
tert-butyl 2-((2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamido)methyl)-7-azaspiro[3.5]nonane-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

61
[ 330786-34-0 ]
N-(7-azaspiro[3.5]nonan-2-ylmethyl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C / Cooling with ice 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

62
[ 330786-34-0 ]
N-benzyl-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C 3: triethylamine / tetrahydrofuran / 5 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1
[2]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

63
[ 330786-34-0 ]
[ 100-46-9 ]
N-benzyl-4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In tetrahydrofuran at 20℃; for 8h;	3.1 (1) Preparation: N-benzyl-4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio) pyrimidine -5-formamide In THF (60 mL) were dissolved 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio) pyrimidine-5-carboxylic acid (1.0 g, 2.95 mmol), benzylamine (379 mg, 3.54 mmol) and HATU(1.35 g, 3.54 mmol). DIEA (1 mL, 5.9 mmol) was added dropwisely. The reaction was conducted at ambient temperature for 8 h, followed by addition of water and extraction with DCM. The organic phase was dried over sodium sulfate. Then the solvent was removed by rotary evaporation. The obtained solid was purified by silica gel column chromatography (DCM / methanol = 50 / 1). The product was N-benzyl-4-((3-chloro-4-methoxybenzyl)amino) -2-(methylthio)pyrimidine-5-formamide as a faint yellow solid (800 mg, yield 63 %).

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1 Location in patent: Paragraph 0194; 0195

64
[ 41965-95-1 ]
[ 330786-34-0 ]

Reference： [1]Patent: EP2886540,2015,A1
[2]Patent: CN104710411,2017,B

65
[ 330786-34-0 ]
4-[(3-chloro-4-methoxybenzyl)amino]-2-(methyl sulfinyl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C
	Multi-step reaction with 2 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C
	Multi-step reaction with 2 steps 1.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / Inert atmosphere; Cooling with ice 1.2: 20 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 0.5 h / -10 - 0 °C

Multi-step reaction with 2 steps 1: triethylamine; dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 6 h / 10 - 15 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 5 - 10 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1
[2]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1
[3]Current Patent Assignee: GUANGZHOU REGENEX CORPORATION CO LTD - CN104059025, 2017, B
[4]Current Patent Assignee: SHANDONG ACAD PHARMACEUTICAL SCIENCES - CN112661705, 2021, A

66
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(3-chloro-4-methoxybenzylamino)-N-(pyrimidine-2-ylmethyl)pyrimidine-5-formamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 60 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.5 h / 0 - 20 °C 3: triethylamine / tetrahydrofuran / Reflux

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

67
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(2-morpholinylethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 18 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

68
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-cycloheptanylpyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

69
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(1-piperidin-4-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

70
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(1-methylpiperidin-4-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2.1: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C 4.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5.1: tetrahydrofuran / 1 h / 20 °C 5.2: 4 h

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

71
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxy benzyl)amino)-N-(trans-4-hydroxycyclohexyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

72
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(((3-chloro-4-methoxybenzyl)amino)pyrimidin-5-yl)(4-methylpiperazin-1-yl)ketone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

73
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-((s)-caprolactam-3-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

74
[ 330786-34-0 ]
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-((7-methyl-7-azaspiro[3.5]nonan-2-yl)methyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 4 h / 20 °C / Cooling with ice 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: sodium tetrahydroborate; methanol / 10 h

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

75
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-N-(trans-4-hydroxycyclohexyl)-2-(5-azaspiro[2.4]heptan-5-yl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / tetrahydrofuran / 18 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

76
[ 330786-34-0 ]
C₂₉H₃₉ClN₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C / Cooling with ice 2: triethylamine / tetrahydrofuran / 5 h / 20 °C / Cooling with ice 3: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / water; tetrahydrofuran / 8 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

77
[ 330786-34-0 ]
C₃₁H₃₇ClN₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 8 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / 20 °C 3: triethylamine / tetrahydrofuran / 4 h / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP2886540, 2015, A1

78
[ 330786-34-0 ]
2-aminomethylpyrimidine methanesulfonate [ No CAS ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylic acid With thionyl chloride In N,N-dimethyl-formamide; toluene for 2.5h; Reflux; Stage #2: 2-aminomethylpyrimidine methanesulfonate With triethylamine In dichloromethane at 15 - 30℃;	3 Referential Example 3 Preparation of 4-[(3-chloro-4-methoxybenzyl) amino]-2-(methyl sulfinyl)-N-(pyrimidin-2-ylmethyl) pyrimidine-5-carboxiamide of Formula(III) To a mixture of 400m1 of toluene and 0.5m1 of dimethylformamide was added 50g of 4-[(3-chloro-4-methoxybenzyl) amino]-2-(methyl sulfanyl) pyrimid ine-5-carboxyl ic acid (Referential Example 2) and 70g of thionyl chloride, and the reaction mixture was refluxed for 2.5 hours. After completion of reaction, solvent was distilled under vacuum and the residue was stripped with toluene to obtain yellow solid mass. The solid mass thus obtained, was cooled to 15-20°C followed by addition of 175m1 of methylene dichioride, 36.lg of 2-amino methyl pyrimidine mesylate and 35.55g of triaethylamine. The reaction mixture was stirred overnight at 25-30°C. After completion of reaction, methylene dichioride was distilled out to get residue. The residue was washed sequentially with 2.5% sodium carbonate solution and water. The residue was then treated with methanol to obtain 4-[(3-chloro-4-methoxybenzyl) amino]-2-(methyl sulfinyl)-N-(pyrimidin-2-ylmethyl) pyrimidine-5 -carboxiamide of Formula (Ill) having HPLC purity of more than 95% (yield: 80%)

Reference： [1]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1 Location in patent: Page/Page column 14; 16

79
[ 330786-34-0 ]
C₂₃H₂₄ClN₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane

Reference： [1]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1

80
[ 330786-34-0 ]
C₂₅H₂₈ClN₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane 4.1: sulfuric acid / Reflux

Reference： [1]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1

81
[ 330786-34-0 ]
C₂₃H₂₃Cl₂N₇O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane 4.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux

Reference： [1]Current Patent Assignee: WANBURY LIMITED - WO2015/177807, 2015, A1

82
[ 372118-67-7 ]
[ 330786-34-0 ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%		Tosyl chloride (254 mg, 1.33 mmol), K2CO3 (538 mg, 3.9 mmol) and compound 21 (500 mg, 1.33 mmol) were added to acetonitrile (10 mL) and stirred at room temperature overnight. Compound 23 (194 mg, 1.33 mmol) was added to the prepared mixed anhydride solution, stirred at room temperature for 20 minutes, and then detected by TLC. The reaction of the starting material was completed. The mixture was diluted with water and washed with ethyl acetate. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated to give compound 24 (601 mg, 95% yield).
1.1 g		The product VII obtained in step (2) (1.0 g) was added to 15 ml of N, N-dimethylformamide, cooled with ice water bath under nitrogen, and HATU (1.67g) was added to the reaction mixture, triethylamine (1.3ml) was added dropwise to the reaction mixture, stirred for 10min, <strong>[372118-67-7]2-aminomethylpyrimidine hydrochloride</strong> (471mg), slowly warmed to 20 ~ 30 C and stirred for 3 ~ 18h. 48 ml of water was added to the reaction solution, the solution became turbid, and a solid precipitated. The solution was extracted with ethyl acetate twice (25 ml × 2). The organic phases were combined, the organic phase was washed twice with 30 ml of 5% sodium carbonate solution, once with 30 ml of water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 1.1 g of a white solid.

Reference： [1]Patent: CN104710411,2017,B .Location in patent: Paragraph 0025; 0075; 0076; 0077; 0078; 0079; 0080-0082
[2]Patent: CN104059025,2017,B .Location in patent: Paragraph 0042; 0043-0045; 0059-0061; 0075-0077; 0091-0093

83
[ 330786-34-0 ]
pyrimidin-2-ylmethanamine hydrochloride [ No CAS ]
4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.1%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In <i>N</i>,<i>N</i>-dimethyl-aniline; N,N-dimethyl-formamide at 60℃; for 7h;	1.5; 2.5; 3.5 S5 4-[(3-Chloro-4-methoxybenzyl)amino]-2-methylthiopyrimidine-5-carboxylic acid (50.1 g, 0.15 mol) obtained in the step S4,2-aminomethylpyrimidine hydrochloride (26.2 g, 0.18 mol),1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride (28.7 g, 0.15 mol),1-hydroxybenzotriazole (22.2 g, 0.15 mol) and triethylamine (18.2,0.18 mol) was added to 150 mL of N,N dimethylformamide and 300 mLIn a mixed solution of N,N dimethylaniline,Warming up to 60 ° C,After reacting for 7 h, the reaction solution was cooled to room temperature and poured into water.Extract with ethyl acetate, then combine the organic phases,The mixture was washed successively with saturated brine (300 mL×3) and saturated sodium hydrogen carbonate solution (300 mL×3), and dried over anhydrous sodium sulfate.The solvent was evaporated under reduced pressure, and the residue was stirred with ethanol for 2 hr, then filtered, and then filtered and washed with ethyl alcohol (150mL×3)Powder (54.3 g, 84.1%),

Reference： [1]Current Patent Assignee: CHINA UNION CHEMPHARMA SUZHOU - CN108707141, 2018, A Location in patent: Paragraph 0027; 0033; 0036; 0042; 0045; 0051

84
[ 53554-29-3 ]
[ 330786-34-0 ]

Reference： [1]Patent: CN108707141,2018,A

85
[ 330786-34-0 ]
C₁₈H₁₇ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine; dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 6 h / 10 - 15 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 5 - 10 °C 3: sodium hydroxide; water / N,N-dimethyl-formamide / 5 h / 20 °C

Reference： [1]Current Patent Assignee: SHANDONG ACAD PHARMACEUTICAL SCIENCES - CN112661705, 2021, A

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CAS No. :	330786-34-0	MDL No. :	MFCD28099353
Formula :	C₁₄H₁₄ClN₃O₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PXYYGISXAWKTCT-UHFFFAOYSA-N
M.W :	339.80	Pubchem ID :	22665572
Synonyms :

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 330786-34-0 ] {[proInfo.proName]}

Quality Control of [ 330786-34-0 ]

Related Doc. of [ 330786-34-0 ]

Product Details of [ 330786-34-0 ]

Safety of [ 330786-34-0 ]

Application In Synthesis of [ 330786-34-0 ]

[ 330786-34-0 ] Synthesis Path-Upstream 1~1

[ 330786-34-0 ] Synthesis Path-Downstream 1~85

Related Functional Groups of
[ 330786-34-0 ]

Aryls

Chlorides

Ethers

Amines

Sulfides

Related Parent Nucleus of
[ 330786-34-0 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 330786-34-0 ] {[proInfo.proName]}

Quality Control of [ 330786-34-0 ]

Related Doc. of [ 330786-34-0 ]

Product Details of [ 330786-34-0 ]

Safety of [ 330786-34-0 ]

Application In Synthesis of [ 330786-34-0 ]

[ 330786-34-0 ] Synthesis Path-Upstream 1~1

[ 330786-34-0 ] Synthesis Path-Downstream 1~85

Related Functional Groups of [ 330786-34-0 ]

Aryls

Chlorides

Ethers

Amines

Sulfides

Related Parent Nucleus of [ 330786-34-0 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 330786-34-0 ]

Related Parent Nucleus of
[ 330786-34-0 ]